The long term objective of this research is to identify the molecular mechanism that accounts for extended lifespan. Two mouse models of extended lifespan will be studied: Caloric restriction and the Ames dwarf mouse. It has been known for decades that caloric restriction in rodents leads to significantly increased lifespan. Likewise, dwarf mice such as the Ames mouse also have a prolonged lifespan. MicroRNAs are likely potential candidates for molecules that regulate lifespan as one of these small RNAs (~22 nt) can control the expression of multiple genes. To determine if miRNAs have a role in aging three specific aims are proposed. Specific aim 1 is to establish the miRNA profile of normal mice at young adulthood, middle age and old age using microarray technology to determine if specific miRNAs correlate with age. miRNA microarray data will be validated by real-time reverse transcriptase PCR. Specific aim 2 will determine the miRNA profile of the long lived caloric restricted mouse to examine if there are specific miRNA correlated with longer lifespan. Specific aim 3 will examine the miRNA profile of the Ames dwarf mouse which is not considered to be a mimetic of caloric restriction. Comparison of the extended lifespan models will indicate if there are specific miRNAs in common that contribute to increased lifespan. The identification of such a regulatory molecule will help unlock the mechanism of controlling lifespan in mammals PUBLIC HEALTH RELEVANCE: Aging is a normal process of life but it is still unknown what mechanism instigates intrinsic aging. If we understand this process, we may be able to delay age- related changes especially those related to age-dependent disease. Understanding models of prolonged lifespan will yield clues into the process and may give insight into how we can age in a more healthy manner.